rs10483810

Variant names:

• chr14-68526257-G-T
• rs10483810
• ENST00000487861.5:c.1036+58007G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000487861.5(RAD51B):​c.1036+58007G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0672 in 152,222 control chromosomes in the GnomAD database, including 451 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.067 (451 hom., cov: 33)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 5 publications found

Genes affected

RAD51B (HGNC:9822): (RAD51 paralog B) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata. [provided by RefSeq, Mar 2016]

RAD51B Gene-Disease associations (from GenCC):

• primary ovarian failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

LOC124903334 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903334	XR_007064222.1	n.11174C>A		non_coding_transcript_exon_variant	Exon 2 of 2
LOC124903334	XR_007064223.1	n.11174C>A		non_coding_transcript_exon_variant	Exon 2 of 3
RAD51B	NM_001321821.2	c.1036+58007G>T		intron_variant	Intron 10 of 10		NP_001308750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1036+58007G>T		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1036+58007G>T		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1036+58007G>T		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10232 AN: 152104 Hom.: 451 Cov.: 33

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.0796

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0672 AC: 10229 AN: 152222 Hom.: 451 Cov.: 33 AF XY: 0.0676 AC XY: 5030 AN XY: 74424

African (AFR) AF: 0.0155 AC: 643 AN: 41544

American (AMR) AF: 0.0559 AC: 855 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3470

East Asian (EAS) AF: 0.00694 AC: 36 AN: 5186

South Asian (SAS) AF: 0.108 AC: 518 AN: 4818

European-Finnish (FIN) AF: 0.101 AC: 1071 AN: 10582

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0922 AC: 6268 AN: 68010

Other (OTH) AF: 0.0787 AC: 166 AN: 2108

Alfa AF: 0.0768 Hom.: 83

Bravo AF: 0.0609

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.70
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10483810; hg19: chr14-68992974;